No predictive biomarkers can robustly identify patients with non–small cell lung cancer (NSCLC) who will benefit from immune checkpoint inhibitor (ICI) therapies. Here, in a machine learning setting, we compared changes (“delta”) in the radiomic texture (DelRADx) of CT patterns both within and outside tumor nodules before and after two to three cycles of ICI therapy. We found that DelRADx patterns could predict response to ICI therapy and overall survival (OS) for patients with NSCLC. We retrospectively analyzed data acquired from 139 patients with NSCLC at two institutions, who were divided into a discovery set (D₁ = 50) and two independent validation sets (D₂ = 62, D₃ = 27). Intranodular and perinodular texture descriptors were extracted, and the relative differences were computed. A linear discriminant analysis (LDA) classifier was trained with 8 DelRADx features to predict RECIST-derived response. Association of delta-radiomic risk score (DRS) with OS was determined. The association of DelRADx features with tumor-infiltrating lymphocyte (TIL) density on the diagnostic biopsies (n = 36) was also evaluated. The LDA classifier yielded an AUC of 0.88 ± 0.08 in distinguishing responders from nonresponders in D₁, and 0.85 and 0.81 in D₂ and D₃. DRS was associated with OS [HR: 1.64; 95% confidence interval (CI), 1.22–2.21; P = 0.0011; C-index = 0.72). Peritumoral Gabor features were associated with the density of TILs on diagnostic biopsy samples. Our results show that DelRADx could be used to identify early functional responses in patients with NSCLC.

BACKGROUND AND PURPOSE: Despite availability of advanced imaging, distinguishing radiation necrosis from recurrent brain tumors noninvasively is a big challenge in neuro-oncology. Our aim was to determine the feasibility of radiomic (computer-extracted texture) features in differentiating radiation necrosis from recurrent brain tumors on routine MR imaging (gadolinium T1WI, T2WI, FLAIR). MATERIALS AND METHODS: A retrospective study of brain tumor MR imaging performed 9 months (or later) post-radiochemotherapy was performed from 2 institutions. Fifty-eight patient studies were analyzed, consisting of a training (n = 43) cohort from one institution and an independent test (n = 15) cohort from another, with surgical histologic findings confirmed by an experienced neuropathologist at the respective institutions. Brain lesions on MR imaging were manually annotated by an expert neuroradiologist. A set of radiomic features was extracted for every lesion on each MR imaging sequence: gadolinium T1WI, T2WI, and FLAIR. Feature selection was used to identify the top 5 most discriminating features for every MR imaging sequence on the training cohort. These features were then evaluated on the test cohort by a support vector machine classifier. The classification performance was compared against diagnostic reads by 2 expert neuroradiologists who had access to the same MR imaging sequences (gadolinium T1WI, T2WI, and FLAIR) as the classifier. RESULTS: On the training cohort, the area under the receiver operating characteristic curve was highest for FLAIR with 0.79; 95% CI, 0.77–0.81 for primary (n = 22); and 0.79, 95% CI, 0.75–0.83 for metastatic subgroups (n = 21). Of the 15 studies in the holdout cohort, the support vector machine classifier identified 12 of 15 studies correctly, while neuroradiologist 1 diagnosed 7 of 15 and neuroradiologist 2 diagnosed 8 of 15 studies correctly, respectively. CONCLUSIONS: Our preliminary results suggest that radiomic features may provide complementary diagnostic information on routine MR imaging sequences that may improve the distinction of radiation necrosis from recurrence for both primary and metastatic brain tumors.

Coronary artery calcium scoring has emerged as a widely available and powerful tool for stratifying cardiovascular risk, predicting outcomes, and guiding preventive therapy in asymptomatic individuals. Coronary artery calcium (CAC) scores obtained from CT scans have been shown to be prognostic in assessment of the risk for development of cardiovascular diseases, facilitating the prediction of out...

(1) Background: Despite the complementarity between radiology and histopathology, both from a diagnostic and a prognostic perspective, quantitative analyses of these modalities are usually performed in disconnected silos. This work presents initial results for differentiating two major non-small cell lung cancer (NSCLC) subtypes by exploring cross-scale associations between Computed Tomography (CT) images and corresponding digitized pathology images. (2) Methods: The analysis comprised three phases, (i) a multi-resolution cell density quantification to identify discriminant pathomic patterns for differentiating adenocarcinoma (ADC) and squamous cell carcinoma (SCC), (ii) radiomic characterization of CT images by using Haralick descriptors to quantify tumor textural heterogeneity as represented by gray-level co-occurrences to discriminate the two pathological subtypes, and (iii) quantitative correlation analysis between the multi-modal features to identify potential associations between them. This analysis was carried out using two publicly available digitized pathology databases (117 cases from TCGA and 54 cases from CPTAC) and a public radiological collection of CT images (101 cases from NSCLC-R). (3) Results: The top-ranked cell density pathomic features from the histopathology analysis were correlation, contrast, homogeneity, sum of entropy and difference of variance; which yielded a cross-validated AUC of 0.72 ± 0.02 on the training set (CPTAC) and hold-out validation AUC of 0.77 on the testing set (TCGA). Top-ranked co-occurrence radiomic features within NSCLC-R were contrast, correlation and sum of entropy which yielded a cross-validated AUC of 0.72 ± 0.01. Preliminary but significant cross-scale associations were identified between cell density statistics and CT intensity values using matched specimens available in the TCGA cohort, which were used to significantly improve the overall discriminatory performance of radiomic features in differentiating NSCLC subtypes (AUC = 0.78 ± 0.01). (4) Conclusions: Initial results suggest that cross-scale associations may exist between digital pathology and CT imaging which can be used to identify relevant radiomic and histopathology features to accurately distinguish lung adenocarcinomas from squamous cell carcinomas.

Tumor vasculature is a key component of the tumor microenvironment that can influence tumor behavior and therapeutic resistance. We present a new imaging biomarker, quantitative vessel tortuosity (QVT), and evaluate its association with response and survival in patients with non–small cell lung cancer (NSCLC) treated with immune checkpoint inhibitor (ICI) therapies. A total of 507 cases were used to evaluate different aspects of the QVT biomarkers. QVT features were extracted from computed tomography imaging of patients before and after ICI therapy to capture the tortuosity, curvature, density, and branching statistics of the nodule vasculature. Our results showed that QVT features were prognostic of OS (HR = 3.14, 0.95% CI = 1.2 to 9.68, P = 0.0006, C-index = 0.61) and could predict ICI response with AUCs of 0.66, 0.61, and 0.67 on three validation sets. Our study shows that QVT imaging biomarker could potentially aid in predicting and monitoring response to ICI in patients with NSCLC.